Tuesday, September 27, 2016

It was not my intention to only write about the Nobel Prize, but I haven't written anything since writing about the Nobel Prize last year. It is the time of the year when the Nobel Prize winners are announced again. I will write my guesses for this year. I was able to guess a win for neutrino oscillations last time. The only major addition for this year is the detection of gravitational waves for the Physics Prize. Keep in mind that the importance of a scientific work does not depend on winning a Nobel Prize. What I'm doing here is a mixture of guessing what the Nobel Committee thinks and expressing what kind of work I want to be recognized.

Physiology or MedicineOptogenetics: Gero Miesenböck, Georg Nagel, and Karl Deisseroth
I'm not a neuroscientist, but I can see why optogenetics may be considered for a Nobel Prize. How the brain functions is a fascinating scientific question and is important for understanding mental illnesses. Optogenetics allows researchers to manipulate neurons by light. It has been used to study which neurons are involved in what kind of processes. That seems pretty cool to me.

Protein chaperones: Arthur Horwich and F. Ulrich Hartl
This is probably a solid pick that has a good chance. It is an important topic in molecular biology. These two scientists have been receiving major awards in a way that is similar to many previous Nobel Prize winners, including the Lasker Award in 2011. They could be considered for the Chemistry Prize, instead.

Transcription machinery in eukaryotes and nuclear hormone receptors: Robert Roeder, Pierre Chambon, and Ronald Evans
Many people seem to be thinking that Evans and Chambon are likely to win the Nobel Prize for the discovery of nuclear hormone receptors. While I don't disagree with the importance of nuclear hormone receptors, I think it is a little weird if Evans and Chambon win while Roeder's more general work on eukaryotic transcription is not recognized. Roeder may have lost his chance when Roger Kornberg was the sole winner of the Chemistry Prize in 2006 for his work on RNA polymerase, but Kornberg won the Chemistry Prize in large part because he solved the structure. There might be a path for the Physiology/Medicine Prize for more biological works of Roeder, Chambon, and Evans together. Both Roeder and Chambon discovered that there are multiple RNA polymerases in eukaryotes. Roeder made many important contributions in the field since then. Evans and Chambon discovered nuclear hormone receptors, which are transcription factors whose activities are dependent on hormones.Paleogenetics: Svante Pääbo
I'm not sure if this is the kind of topic that the Nobel Prize will recognize, but I think this is a very exciting field.

I don't know any other recent technique that has had as huge an impact in biomedical sciences as CRISPR has. Optogenetics is cool, but it is a method used in a more specialized field. CRISPR is used in a wide range of fields. In that regard, CRISPR is an obvious choice for a Nobel Prize. The only problem is that it is not easy to choose the recipients.

The biggest impact of CRISPR on research has been for genome editing. The use of CRISPR for genome editing was first demonstrated by the laboratories of Feng Zhang and George Church. (One may also include a paper published by Jennifer Doudna's laboratory shortly after them.) There is no question that their papers were excellent and highly influential. But one can argue that someone else with experience in zinc-finger nucleases or TALENs would have accomplished this sooner or later if they had not.

The genome editing technique is dependent on the enzymatic activity of Cas9, which was demonstrated in one paper by Jennifer Doudna and Emmanuelle Charpentier's laboratories, and in another paper by Virginijus Siksnys' laboratory. But one can argue that even their findings could be anticipated from earlier studies that had shown that CRISPR targets DNA.

If you want to credit the discovery of CRISPR as an adaptive immune system, that was demonstrated by Rodolphe Barrangou, Philippe Horvath and others. But even that was anticipated by bioinformatic analyses and predictions made in one paper by Alexander Bolotin and the colleagues, and in another paper by Eugene Koonin and the colleagues. The pioneering studies by Francisco Mojica and others were indispensable, even though they were not the ones who ended up solving the puzzle and therefore are unlikely to receive the Nobel Prize.

Researchers who have received various major awards for CRISPR-related work include Rodolphe Barrangou, Emmanuelle Charpentier, Jennifer Doudna, Philippe Horvath, Virginijus Siksnys, and Feng Zhang. Oddly, George Church has not received an award for this, as far as I know. Church runs a huge lab and it's possible the his personal contribution was not big. Still, it's weird that no one from his group was given a credit while Zhang was.

Scientific progress depends on contributions by many people. CRISPR is a great example. We wouldn't be talking about CRISPR now without the people who were studying those odd sequences in bacteria when it was not fashionable to do so. But they are not likely to win the Nobel Prize. Whoever is chosen as the recipient for the CRISPR work, there will be some controversy. Someone could be disappointed because she or he was not chosen as the recipient in spite of doing an important work. A situation like this makes me uncomfortable about the Nobel Prize. I concede that, by trying to guess the winners, I am guilty of treating the Nobel Prize like it is a big deal.

As I have written before, there has been a revolution in cryo-electron microscopy. The resolution has improved and I have seen many important structures solved using this technique. The impact is undeniable.

Chemical biology: Stuart Schreiber

Schreiber's group has done many things. They made important findings related to calcineurin, rapamycin, histone deacetylases, among other things. These are hot topics, but there are other important researchers in each field and Schreiber's group tends to move to new things instead of becoming the specialist. The Nobel Prize is not supposed to be a lifetime achievement award. Is it possible to single out one thing Schreiber's group did that deserves a Nobel Prize? Or is it possible to honor him as a pioneer in chemical biology, which uses chemistry, especially small molecules, to make important biological discoveries? These questions are up for debate. I can easily picture him winning the prize because of the impacts of what he has done, but I won't be surprised if he doesn't.

Histone modifications: David Allis
Histones are proteins that for a long time were considered boring packing materials that make up chromosomes. There were some people, most notably Vincent Allfrey, who thought that chemical modifications of histones are important for regulating gene expression, but there was not a definitive evidence. Things changed in 1996. That year, David Allis' group discovered an enzyme that add acetyl groups to histones (histone acetylase) and Stuart Schreiber's group discovered an enzyme that remove acetyl groups from histones (histone deacetylase). Importantly, the yeast homolog of the histone acetylase was known to activate gene expression and the yeast homolog of the histone deacetylase was known to repress gene expression. That supported the connection between histone modifications and gene expression. Exciting developments followed.

For Schreiber, that was just one of many things his group did. They haven't done much in the field since then. Allis, on the other hand, has followed up on that discovery by doing many important works in the field. There has been some unfortunate overhyping of the field and Allis is probably guilty of doing some of that. Nevertheless, I do think that the field is very exciting and important. This could be a topic for the Physiology/Medicine Prize, but I thought that the discovery of the histone acetylase by Allis' group could be paired with the discovery of the histone deacetylse by Schreiber's group.

Protein chaperones: Arthur Horwich and F. Ulrich Hartl
Many of the candidates for the Physiology/Medicine Prize also have a chance of winning the Chemistry Prize. Protein chaperones are particularly chemical among them.

If there is a Chemistry Prize for CRISPR instead of a Physiology/Medicine Prize, these three could be the recipients for showing that Cas9 is an RNA-guided enzyme that cuts DNA.

PhysicsDetection of gravitational waves: Rainer Weiss, Kip Thorne, and Ronald Drever
This is probably as close to a shoo-in to win the Physics Prize as possible. There is no question about the importance of the discovery. It has received a huge publicity. There are three consensus choice for the recipients. I can't think of a reason why this will not win a Nobel Prize. The only question is whether it is going to be this year. The announcement of the detection was made on February 11th of this year. Was there enough time for nomination to be considered for this year's prize? Perhaps it does not matter because the committee should be aware of the news. But only two events have been reported so far. It won't surprise me if the committee wants to wait a little longer for more validation. But it's quite possible that they will award the Physics Prize for gravitational waves this year.

Like many important discoveries in physics, this was done by a huge collaboration that involves more than a thousand people. I think that the rule of only recognizing up to three representatives is unfair and outdated. But this is not something that the Nobel Committee is going to change this year.

I have been guessing that this will win the Physics Prize for years. This is arguably as important as gravitational waves. However, it may not be quite a shoo-in to win the Nobel Prize like the detection of gravitational waves. It has a long and complicated history involving many people and it may be difficult to narrow down to three winners. The one who has made the most important contribution, John Bell, has died a few decades ago. There were concerns about possible loopholes in the experimental tests of Bell's inequalities. Since last year, loophole-free Bell tests have been reported. This on one hand strengthen the case for a Nobel Prize for this subject, but on the other hand complicates the situation by adding even more names. It is possible that the Nobel Prize will go to other topics related to quantum information such as quantum teleportation, just like the 2012 Prize went to different works related to quantum measurements.